• Title/Summary/Keyword: protein-protein network

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Protein Interaction Network Visualization System Combined with Gene Ontology (유전자 온톨로지와 연계한 단백질 상호작용 네트워크 시각화 시스템)

  • Choi, Yun-Kyu;Kim, Seok;Yi, Gwan-Su;Park, Jin-Ah
    • Journal of KIISE:Computer Systems and Theory
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    • v.36 no.2
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    • pp.60-67
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    • 2009
  • Analyzing protein-protein interactions(PPI) is an important task in bioinformatics as it can help in new drugs' discovery process. However, due to vast amount of PPI data and their complexity, efficient visualization of the data is still remained as a challenging problem. We have developed efficient and effective visualization system that integrates Gene Ontology(GO) and PPI network to provide better insights to scientists. To provide efficient data visualization, we have employed dynamic interactive graph drawing methods and context-based browsing strategy. In addition, quick and flexible cross-reference system between GO and PPI; LCA(Least Common Ancestor) finding for GO; and etc are supported as special features. In terms of interface, our visualization system provides two separate graphical windows side-by-side for GO graphs and PPI network, and also provides cross-reference functions between them.

Network Analyses of Gene Expression following Fascin Knockdown in Esophageal Squamous Cell Carcinoma Cells

  • Du, Ze-Peng;Wu, Bing-Li;Xie, Jian-Jun;Lin, Xuan-Hao;Qiu, Xiao-Yang;Zhan, Xiao-Fen;Wang, Shao-Hong;Shen, Jin-Hui;Li, En-Min;Xu, Li-Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5445-5451
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    • 2015
  • Fascin-1 (FSCN1) is an actin-bundling protein that induces cell membrane protrusions, increases cell motility, and is overexpressed in various human epithelial cancers, including esophageal squamous cell carcinoma (ESCC). We analyzed various protein-protein interactions (PPI) of differentially-expressed genes (DEGs), in fascin knockdown ESCC cells, to explore the role of fascin overexpression. The node-degree distributions indicated these PPI sub-networks to be characterized as scale-free. Subcellular localization analysis revealed DEGs to interact with other proteins directly or indirectly, distributed in multiple layers of extracellular membrane-cytoskeleton/ cytoplasm-nucleus. The functional annotation map revealed hundreds of significant gene ontology (GO) terms, especially those associated with cytoskeleton organization of FSCN1. The Random Walk with Restart algorithm was applied to identify the prioritizations of these DEGs when considering their relationship with FSCN1. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile following fascin knockdown to future examine the roles and mechanisms of fascin action.

Thermostability prediction of protein structure by using elastic network model (탄성망모델을 이용한 단백질 열안정성 해석)

  • Park, Young-Gul;Won, Chong-Jin;Jeong, Jay-I.
    • Proceedings of the KSME Conference
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    • 2008.11a
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    • pp.1643-1646
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    • 2008
  • In this study, an elastic network model is established in order to find dominant factors which reflect thermostability of protein structures. The connections in the elastic network model are selected with respect to the free energy between alpha-carbons, which is representatives of residues in the elastic network model. We carried out normal mode analysis and compared eigenvalues of the stiffness matrix from the elastic network model. In most cases, thermophilic proteins are observed to have higher values of lowest natural frequency than mesophiles and psychrophiles have. As a result, the thermophiles are calculated to be stiffer than other proteins in view of dynamic vibration.

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Enhanced Induction of T Cell Immunity Using Dendritic Cells Pulsed with HIV Tat and HCMV-pp65 Fusion Protein In Vitro

  • Park, Jung-Sun;Park, Soo-Young;Cho, Hyun-Il;Sohn, Hyun-Jung;Kim, Tai-Gyu
    • IMMUNE NETWORK
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    • v.11 no.3
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    • pp.182-189
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    • 2011
  • Background: Cytotoxic T lymphocytes (CTLs) appear to play an important role in the control and prevention of human cytomegalovirus (HCMV) infection. The pp65 antigen is a structural protein, which has been defined as a potential target for effective immunity against HCMV infection. Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (Tat) into protein facilitates rapid, efficient entry into cells. Methods: To establish a strategy for the generation of HCMV-specific CTLs in vitro, recombinant truncated N- and C-terminal pp65 protein (pp65 N&C) and N- and C-terminal pp65 protein fused with Tat (Tat/pp65 N&C) was produced in E.coli system. Peripheral blood mononuclear cells were stimulated with dendritic cells (DCs) pulsed with pp65 N&C or Tat/pp65 N&C protein and immune responses induced was examined using IFN-${\gamma}$ ELISPOT assay, cytotoxicity assay and tetramer staining. Results: DCs pulsed with Tat/pp65N&C protein could induce higher T-cell responses in vitro compared with pp65N&C. Moreover, the DCs pulsed with Tat/pp65 N&C could stimulate both of $CD8^+$ and $CD4^+$ T-cell responses. The T cells induced by DCs pulsed with Tat/pp65 N&C showed higher cytotoxicity than that of pp65-pulsed DCs against autologous lymphoblastoid B-cell line (LCL) expressing the HCMV-pp65 antigen. Conclusion: Our results suggest that DCs pulsed with Tat/pp65 N&C protein effectively induced pp65-specific CTL in vitro. Tat fusion recombinant protein may be useful for the development of adoptive T-cell immunotherapy and DC-based vaccines.

Computational approaches for prediction of protein-protein interaction between Foot-and-mouth disease virus and Sus scrofa based on RNA-Seq

  • Park, Tamina;Kang, Myung-gyun;Nah, Jinju;Ryoo, Soyoon;Wee, Sunghwan;Baek, Seung-hwa;Ku, Bokkyung;Oh, Yeonsu;Cho, Ho-seong;Park, Daeui
    • Korean Journal of Veterinary Service
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    • v.42 no.2
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    • pp.73-83
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    • 2019
  • Foot-and-Mouth Disease (FMD) is a highly contagious trans-boundary viral disease caused by FMD virus, which causes huge economic losses. FMDV infects cloven hoofed (two-toed) mammals such as cattle, sheep, goats, pigs and various wildlife species. To control the FMDV, it is necessary to understand the life cycle and the pathogenesis of FMDV in host. Especially, the protein-protein interaction between FMDV and host will help to understand the survival cycle of viruses in host cell and establish new therapeutic strategies. However, the computational approach for protein-protein interaction between FMDV and pig hosts have not been applied to studies of the onset mechanism of FMDV. In the present work, we have performed the prediction of the pig's proteins which interact with FMDV based on RNA-Seq data, protein sequence, and structure information. After identifying the virus-host interaction, we looked for meaningful pathways and anticipated changes in the host caused by infection with FMDV. A total of 78 proteins of pig were predicted as interacting with FMDV. The 156 interactions include 94 interactions predicted by sequence-based method and the 62 interactions predicted by structure-based method using domain information. The protein interaction network contained integrin as well as STYK1, VTCN1, IDO1, CDH3, SLA-DQB1, FER, and FGFR2 which were related to the up-regulation of inflammation and the down-regulation of cell adhesion and host defense systems such as macrophage and leukocytes. These results provide clues to the knowledge and mechanism of how FMDV affects the host cell.

Laminin-1 Phosphorylation by Protein Kinase A: Effect on self assembly and heparin binding

  • Koliakos, George;Kouzi-Koliakos, Kokkona;Triantos, Athanasios;Trachana, Varvara;Kavoukopoulos, Evaggelos;Gaitatzi, Mary;Dimitriadou, Aphrodite
    • BMB Reports
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    • v.33 no.5
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    • pp.370-378
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    • 2000
  • Incubation of purified laminin1-nidogen1 complexes with $[{\gamma}-^{32}P]-ATP$ in the presence of the catalytic subunit of the protein kinase A (cAMP-dependent protein kinase) resulted in the phosphorylation of the alpha chain of laminin-1 and of the nidogen-1 molecule. Aminoacid electrophoresis indicated that phosphate was incorporated on serine residues. The phosphorylation effect of laminin-1 on the process of self assembly was studied by turbidometry. In these experiments, the phosphorylated laminin-1 showed a reduced maximal aggregation capacity in comparison to the non-phosphorylated molecule. Examination of the laminin-1 network under the electron microscope showed that the phosphorylated sample formed mainly linear extended oligomers, in contrast to controls that formed large and dense multimeric aggregates. Heparin binding on phosphorylated laminin-1 in comparison to controls was also tested using solid-phase binding assays. The results indicated an enhanced heparin binding to the phosphorylated protein. The results of this study indicate that laminin1-nidogen1 is a substrate for protein kinase A in vitro. This phosphorylation had an obvious influence on the lamininl-nidogen1 network formation and the heparin binding capacity of this molecule. However, further studies are needed to investigate whether or not this phenomenon could play a role in the formation of the structure of basement membranes in vivo.

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Evolutionary Analyses of Hanwoo (Korean Cattle)-Specific Single-Nucleotide Polymorphisms and Genes Using Whole-Genome Resequencing Data of a Hanwoo Population

  • Lee, Daehwan;Cho, Minah;Hong, Woon-young;Lim, Dajeong;Kim, Hyung-Chul;Cho, Yong-Min;Jeong, Jin-Young;Choi, Bong-Hwan;Ko, Younhee;Kim, Jaebum
    • Molecules and Cells
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    • v.39 no.9
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    • pp.692-698
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    • 2016
  • Advances in next generation sequencing (NGS) technologies have enabled population-level studies for many animals to unravel the relationships between genotypic differences and traits of specific populations. The objective of this study was to perform evolutionary analysis of single nucleotide polymorphisms (SNP) in genes of Korean native cattle Hanwoo in comparison to SNP data from four other cattle breeds (Jersey, Simmental, Angus, and Holstein) and four related species (pig, horse, human, and mouse) obtained from public databases through NGS-based resequencing. We analyzed population structures and differentiation levels for the five cattle breeds and estimated species-specific SNPs with their origins and phylogenetic relationships among species. In addition, we identified Hanwoo-specific genes and proteins, and determined distinct changes in protein-protein interactions among five species (cattle, pig, horse, human, mouse) in the STRING network database by additionally considering indirect protein interactions. We found that the Hanwoo population was clearly different from the other four cattle populations. There were Hanwoo-specific genes related to its meat trait. Protein interaction rewiring analysis also confirmed that there were Hanwoo-specific protein-protein interactions that might have contributed to its unique meat quality.

Stage specific transcriptome profiles at cardiac lineage commitment during cardiomyocyte differentiation from mouse and human pluripotent stem cells

  • Cho, Sung Woo;Kim, Hyoung Kyu;Sung, Ji Hee;Han, Jin
    • BMB Reports
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    • v.54 no.9
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    • pp.464-469
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    • 2021
  • Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived platelet-derived growth factor receptor-alpha (PDGFRα)+ cardiac lineage-committed cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)+ and PDGFRα+ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K-AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα+ CLCs and hiPSC-derived KDR+PDGFRα+ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases.

Proteomic Analysis of Resting and Activated Human $CD8^+$ T Cells

  • Koo Jung-Hui;Chae Wook-Jun;Choi Je-Min;Nam Hyung-Wook;Morio Tomohiro;Kim Yu-Sam;Jang Yang-Soo;Choi Kwan-Yong;Yang Jung-Jin;Lee Sang-Kyou
    • Journal of Microbiology and Biotechnology
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    • v.16 no.6
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    • pp.911-920
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    • 2006
  • [ $CD8^+$ ] T Iymphocytes with the cytotoxic activity and capability to release various cytokines are the major players in immune responses against viral infection and cancer. To identify the proteins specific to resting or activated human CD8$^+$ T cells, human CD8$^+$ T cells were activated with anti-CD3+anti-CD28 mAb in the presence of IL-2. The solubilized proteins from resting and activated human CD8$^+$ T cells were separated by high-resolution two-dimensional polyacrylamide gel electrophoresis, and their proteomes were analyzed. Proteomic analysis of resting and activated T cells resulted in identification of 35 proteins with the altered expression. Mass spectrometry coupled with Profound and SWISS-PROT database analysis revealed that these identified proteins are to be functionally associated with cell proliferation, metabolic pathways, antigen presentation, and intracellular signal transduction pathways. We also identified six unknown proteins predicted from genomic DNA sequences specific to resting or activated CD8$^+$ T cells. Protein network studies and functional characterization of these novel proteins may provide new insight into the signaling transduction pathway of CD8$^+$ T cell activation.

NMR Studies on Turn Mimetic Analogs Derived from Melanocyte-stimulating Hormones

  • Cho, Min-Kyu;Kim, Sung-Soo;Lee, Myung-Ryul;Shin, Joon;Lee, Ji-Yong;Lim, Sung-Kil;Baik, Ja-Hyun;Yoon, Chang-Ju;Shin, In-Jae;Lee, Weon-Tae
    • BMB Reports
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    • v.36 no.6
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    • pp.552-557
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    • 2003
  • Oligomers with $\alpha$-aminooxy acids are reported to form very stable turn and helix structures, and they are supposed to be useful peptidomimetics for drug design. A recent report suggested that homochiral oxa-peptides form a strong eight-member-ring structure by a hydrogen bond between adjacent aminooxy-acid residues in a $CDCl_3$ solution. In order to design an $\alpha$-MSH analog with a stable turn conformation, we synthesized four tetramers and one pentamer, based on $\alpha$-MSH sequence, and determined the solution structures of the molecules by two-dimensional NMR spectroscopy and simulated annealing calculations. The solution conformations of the three peptidomimetic molecules (TLV, TDV, and TLL) in DMSO-$d_6$ contain a stable 7-membered-ring structure that is similar to a $\gamma$-turn in normal peptides. Newly-designed tetramer TDF and pentamer PDF have a ball-type rigid structure that is induced by strong hydrogen bonds between adjacent amide protons and carbonyl oxygens. In conclusion, the aminooxy acids, easily prepared from natural or unnatural amino acids, can be employed to prepare peptidomimetic analogues with well-defined turn structures for pharmaceutical interest.